[Federal Register Volume 71, Number 28 (Friday, February 10, 2006)]
[Notices]
[Pages 7048-7051]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-1806]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004D-0369]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Recommendations for 
the Early Food Safety Evaluation of New Non-Pesticidal Proteins 
Produced by New Plant Varieties Intended for Food Use

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Notice.

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SUMMARY:  The Food and Drug Administration (FDA) is announcing that a 
proposed collection of

[[Page 7049]]

information has been submitted to the Office of Management and Budget 
(OMB) for review and clearance under the Paperwork Reduction Act of 
1995 (the PRA).

DATES:  Fax written comments on the collection of information by March 
13, 2006.

ADDRESSES: OMB is still experiencing significant delays in the regular 
mail, including first class and express mail, and messenger deliveries 
are not being accepted. To ensure that comments on the information 
collection are received, OMB recommends that comments be faxed to the 
Office of Information and Regulatory Affairs, OMB, Attn: Fumie Yokota, 
Desk Officer for FDA, FAX: 202-395-6974.

FOR FURTHER INFORMATION CONTACT:  Jonna Capezzuto, Office of Management 
Programs (HFA-250), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-827-4659.

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Recommendations for the Early Food Safety Evaluation of New Non-
Pesticidal Proteins Produced by New Plant Varieties Intended for Food 
Use

    Since 1992, when FDA issued its Statement of Policy: Foods Derived 
from New Plant Varieties (57 FR 22984, May 29, 1992), FDA has 
encouraged developers of new plant varieties, including those varieties 
that are developed through biotechnology, to consult with FDA early in 
the development process to discuss possible scientific and regulatory 
issues that might arise. The current guidance continues to foster early 
communication by encouraging developers to submit to FDA their 
evaluation of the food safety of their new protein. Such communication 
helps to ensure that any potential food safety issues regarding a new 
protein in a new plant variety are resolved early in development, prior 
to any possible inadvertent introduction into the food supply of 
material from that plant variety.
    FDA believes that any food safety concern related to such material 
entering the food supply would be limited to the potential that a new 
protein in food from the plant variety could cause an allergic reaction 
in susceptible individuals or could be a toxin. This guidance describes 
the procedures for early food safety evaluation of new proteins in new 
plant varieties, including bioengineered food plants, and the 
procedures for communicating with FDA about the safety evaluation.
    In the Federal Register of November 24, 2004 (69 FR 68381), FDA 
published a notice of availability with a 60-day comment period 
requesting public comment on the collection of information in FDA's 
draft guidance document titled, ``Guidance for Industry: 
Recommendations for the Early Food Safety Evaluation of New Non-
Pesticidal Proteins Produced by New Plant Varieties Intended for Food 
Use.''

Nonresponsive comments

    FDA received approximately 5,000 letters in response to the 
November 24, 2004, notice. However, many of these letters contained 
comments that were not responsive to the PRA questions. For example, 
several comments expressed the following opinions: The collection of 
information was insufficient to ensure safety; the agency might not be 
able to commit sufficient resources to performing early food safety 
reviews without having to redirect resources from other tasks; the 
decision should not be left to the developer regarding when to submit 
an early food safety evaluation to the agency; and the objectivity and 
scientific expertise of the individuals reviewing the information may 
be inadequate.
    (Response) These comments are general comments directed to the 
adequacy of the guidance, rather than specific comments relevant to the 
collection of information; therefore, these non-responsive comments 
will not be addressed in this document.

Responsive comments

    FDA received several letters with specific comments responsive to 
the comment request concerning the proposed information collection in 
the notice. The comments and FDA's responses follow.
    (Comment 1) Several comments were supportive of the information 
collection, stating that the information collection was necessary for 
FDA to fulfill statutory requirements to protect the safety of the food 
supply. Relevant to the minimization of burden, several of these 
comments also noted that the information collection was appropriately 
limited in scope to prevent duplicative submissions among Federal 
agencies.
    (Response) These comments provide support for the utility of the 
information collection and confirm that the collection will not result 
in a duplicative information collection among Federal agencies.
    (Comment 2) One comment suggested that FDA should minimize the 
burden on developers by referencing in the guidance the availability of 
public protein databases that could be useful in the evaluation of 
allergen or toxin homology.
    (Response) FDA does not want to reference or list the various 
databases because to do so would imply that FDA is endorsing any or all 
of them. FDA finds that there are several databases in the public 
domain that are easily obtained through the internet, are known in the 
scientific community, and are in common use by developers of 
bioengineered crops.
    (Comment 3) One comment suggested that FDA could minimize the 
burden of the proposed collection of information by clarifying that a 
weight of the evidence approach is applied to the assessment of 
potential allergenicity of a new protein. The comment further suggested 
that alternative methods and protocols be considered in the evaluation 
of the allergenicity of new proteins.
    (Response) FDA's guidance does not state that a weight of the 
evidence approach will be applied to the evaluation. The guidance 
describes a case-by-case evaluation that recognizes that different 
pieces of information may have varying importance for the food safety 
evaluation depending on the characteristics of the protein. As stated 
in the guidance, developers are free to use alternative approaches in 
their evaluations. The comment fails to explain how a weight of the 
evidence approach would reduce the burden under the PRA.
    (Comment 4) One comment suggested as an approach to minimize burden 
on developers that FDA treat highly similar proteins as a family of 
proteins, if they differ only by a few amino acids but retain the same 
function, rather than evaluating each protein individually, though the 
comment further suggests that certain aspects of a protein may be 
evaluated individually.
    (Response) FDA notes that the guidance is intended to consider 
specific proteins, not protein families. FDA further notes that even 
small changes in amino acid sequence may alter a protein, and these 
small differences could also have implications for food safety. 
However, if there is relevant information contained in a previous 
submission, that information can be incorporated by reference into a 
current submission for a new protein evaluation.
    (Comment 5) One comment suggested as a means of minimizing burden 
of the proposed collection of information that

[[Page 7050]]

FDA provide standard forms or formats for certain elements of the 
submission (e.g., bioinformatics reports). The comment also suggested 
minimizing burden by making greater use of electronic submissions.
    (Response) FDA has considered the use of standardized forms or 
formats and at this time does not believe that their use would reduce 
the burden of the information collection. The use of standardized forms 
could discourage alternative approaches for the presentation of data in 
an evaluation that might more clearly or thoroughly set forth the data. 
Developers will have access to the forms and formats used by previous 
submitters and are free to use them; thus, at this time we do not 
perceive a need for a standardized form. Based on its experience in 
evaluation of submissions FDA will in the future revisit whether the 
use of standardized forms and formats would be advantageous to 
developers.
    With respect to electronic submissions, FDA states in the guidance 
that electronic submissions are acceptable, but one paper copy is also 
requested. Efforts are underway at FDA to convert in the future to a 
submission process that is entirely electronic.
    (Comment 6) One comment stated that a way to enhance the quality, 
utility, and clarity of the information to be collected is to follow 
guidance available from the Codex Alimentarius. Although the comment 
did not specify which guidance from the Codex Alimentarius FDA should 
follow, FDA believes that the comment is referring to the Codex 
Alimentarius ``Guideline for the Conduct of Food Safety Assessment of 
Foods Derived from Recombinant-DNA Plants'' (CAC/GL 45-2003) (the Codex 
Plant Guideline), containing ``Annex: Assessment of Possible 
Allergenicity'' (the Codex Allergenicity Annex). The comment also 
stated that FDA should make Codex guidance a mandatory part of its 
guidance.
    (Response) FDA agrees in part and disagrees in part. FDA notes that 
its recommendations in this guidance are consistent with the approach 
recommended in the Codex Plant Guideline. In fact, FDA references the 
Codex Plant Guideline as a resource to be consulted by a developer in 
evaluating the food safety of a new protein. However, FDA notes that 
the Codex Plant Guideline addresses a broad range of issues associated 
with food safety assessment of food derived from bioengineered plants. 
While FDA's guidance is consistent with the Codex Plant Guideline, it 
does not address the entire broad range of issues as that document. 
FDA's guidance is focused on the food safety issues that might arise 
from the intermittent, low-level presence of material from a plant 
being developed for food and feed use. FDA believes that any potential 
risk from the intermittent, low level presence of such material in the 
food supply would be limited to the food safety of the new proteins. 
FDA references the Codex Plant Guideline, paragraphs 34-43 under 
Expressed Substances (non-nucleic acid substances) and the Codex 
Allergenicity Annex, for that component of the safety review.
    FDA disagrees with the comment's suggestion that the agency make 
the Codex Plant Guideline a mandatory part of its guidance. While FDA 
believes that the Codex Plant Guideline and the Codex Allergenicity 
Annex are useful documents, it recognizes that other approaches may 
also be appropriate.
    (Comment 7) One comment stated that while the information to be 
collected is essential and important for FDA to obtain, the information 
is inadequate to fulfill FDA's ``stated and mandated goals,'' and 
therefore it is of questionable utility.
    (Response) FDA disagrees. The guidance is properly focused on the 
food safety assessment of a new protein produced in a new plant variety 
when there might be a low level, intermittent presence of material from 
a plant being developed for food. Although the commenter would like 
more information to be presented for FDA review at this stage, FDA 
notes that more information is not necessary because the information 
that the guidance recommends a developer collect and present to FDA as 
part of a food safety evaluation of a protein is adequate for the 
specific assessment that FDA is making at this stage. FDA recommends 
that a broader scope of information be presented to FDA for review at 
subsequent evaluation stages. For example, when a developer utilizes 
the recommendations articulated in FDA's guidance entitled, 
``Consultation Procedures for New Plant Varieties'' (available at 
http://www.cfsan.fda.gov/~lrd/consulpr.html), FDA expects that 
significantly more information will be presented during the 
consultation.
    (Comment 8) Several comments challenged the accuracy of FDA's 
estimate of the burden of the proposed collection of information. These 
comments opined that FDA should collect more extensive information than 
what is proposed in the guidance, and they concluded, therefore, that 
FDA had underestimated the burden of the proposed information 
collection. The comments did not challenge the accuracy of the burden 
estimate for the information as proposed in the guidance.
    (Response) FDA notes that the comments did not challenge the 
accuracy of FDA's estimate, rather they challenged what FDA recommends 
in the guidance. FDA believes that the estimate of the burden of the 
proposed collection of information is accurate.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 1.--Estimated Annual Reporting Burden\1\
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                                                                   Annual Frequency per        Total Annual
                                         No. of Respondents              Response                Responses        Hours Per Response      Total Hours
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First four data components                                  20                          1                    20                     4                 80
Two other data components                                   20                          1                    20                    16                320
Total                                .........................  .........................  ....................  ....................                400
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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.

One Time Burden

    Completing an early food safety evaluation for a new protein from a 
new plant variety will be a one-time burden (one evaluation per new 
protein). FDA cannot know how many developers will choose to complete 
an early food safety evaluation for their new plant protein. Many 
developers of novel plants may choose not to submit an evaluation 
because the field testing of a plant containing a new protein is 
conducted

[[Page 7051]]

in such a way (e.g., on such a small scale, or in such isolated 
conditions, etc.) that cross-pollination with traditional crops or 
commingling of plant material is not likely to be an issue. Also, other 
developers may have previously communicated with FDA about the food 
safety of a new plant protein, for example, when the same protein was 
expressed in a different crop.
    FDA scientists predict that this draft guidance will generate about 
20 to 150 early food safety evaluations yearly. While there is 
uncertainty as to the number of developers who will choose to submit an 
evaluation, FDA estimates that the annual number of early food safety 
evaluations will be closer to the lower bound estimate of 20 
evaluations rather than the upper bound estimate of 150 evaluations. 
This estimation is supported by the fact that on average there have 
been nine initial biotechnology consultations per year. An initial 
biotechnology consultation has traditionally been the first discussion 
between a developer and FDA about a food made from a new bioengineered 
plant variety; it is usually bioengineered varieties of plants that are 
the subject of a consultation with FDA.

Evaluation Components

    The early food safety evaluation for new proteins includes six main 
data components. Four of these data components are easily and quickly 
obtainable, having to do with the identity and source of the protein. 
FDA estimates that completing these data components will take about 4 
hours per evaluation. In table 1 of this document, row 1 shows that for 
20 evaluations, the total burden for these 4 data components is 80 
hours.
    Two data components ask for original data to be generated. One data 
component consists of a bioinformatics analysis which can be performed 
using publicly available databases. The other data component involves 
`wet' lab work to assess the new protein's stability and the resistance 
of the protein to enzymatic degradation using appropriate in vitro 
assays (protein digestibility study).
    The paperwork burden of these two data components consists of the 
time it takes the company to put together the information on these two 
data components to submit to FDA. We estimate that these two data 
components will take 16 hours to complete (8 hours for each component). 
In Table 1 of this document, row 2 shows that for 20 evaluations, the 
total burden for these two data components is 320 hours.

    Dated: February 6, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-1806 Filed 2-9-06; 8:45 am]
BILLING CODE 4160-01-S